Approximately 9-15 million smokers in the U.S. meet criteria for at least one anxiety disorder during their lifetime (Kessler et al., 2005) and these persons experience significant challenges quitting tobacco (Piper et al., 2010a; Zvolensky et al., 2008). Yet, little attention has been given to the maintenance of tobacco use among persons with anxiety disorders, and in particular, smokers with a history of panic attacks. This group is especially important to study because research shows that they have significantly lower quit rates than smokers with no history of panic attacks, and that they respond the same to placebo, single cessation, and combination cessation pharmacotherapy (Piper et al., 2010a). The goal of the current research is to pilot test the efficacy of the addition of d-cycloserine (DCS) versus pil placebo to a cognitive-behavioral program (CBT) targeting the role of anxiety sensitivity, distress intolerance, and panic attacks in smoking maintenance. The proposed project builds directly from our basic and clinical research as well as corresponding pilot work on (a) tobacco-panic relations; (b) intensive cognitive-behavioral intervention (CBT) for panic- and anxious-prone smokers; and (c) DCS enhancement of CBT for panic reduction. The project aims to obtain initial effect sizes and perform an initial test of putative mechanisms of our specialized behavioral group protocol, Panic and Smoking Reduction Treatment (PSRT), combined with DCS as compared to PSRT plus placebo. The PSRT program integrates interceptive exposure, cognitive restructuring, and psycho education exercises with standard smoking cessation strategies and nicotine replacement therapy. Adult smokers (n = 80) with panic attacks will be recruited and randomly assigned to either: (1) PSRT plus DCS or (2) PSRT plus pill placebo. Primary outcome measures will be point prevalence abstinence, time to first smoking lapse, and time to smoking relapse, assessed at 2, 4, 8, 10, 16, and 24 weeks after quit date. Proposed mediators include panic attacks, distress intolerance, anxiety sensitivity, nicotine withdrawal symptoms, and negative effect. These variables will be assessed at baseline, weekly during the treatment phase, and at 2, 4, 8, 10, 16, and 24 weeks after quit date. The proposed study represents a crucial and important stage in translating basic research to strategies for treating nicotine dependence. The investigation addresses an important public health issue by testing an integrated intervention --- informed by basic research --- that may lead to a more effective and efficient treatment for at-risk smokers while simultaneously isolating explanatory mechanisms. The expected findings should: (1) guide advances in the theoretical conceptualization of the mechanisms involved in panic- and anxiety-smoking relations; and (2) provide initial effect size data for the addition of DCS to an integrated psychosocial/behavioral and pharmacological smoking cessation intervention for smokers with panic attacks, and thus provide the necessary data for a large-scale follow-up trial.